This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Obesity is one of the major health risk facing the developed world, significantly increasing the risk of coronary disease, and of diabetes. It has recently been shown that for every "point" by which a person's body mass index (BMI) exceeds 25, there is an associated increase (5% in men and 7% in women) in the risk of cardiac disease. Beyond the terrible human costs there are significant economic costs associated with health care for such an obese population. An estimated 9.4% of US healthcare expenditure is directly related to "obesity and inactivity", while recent costs due to diabetes were estimated at $98 billion per annum. There are two main aims of this study: Phase 1 will determine the efficacy of peripheral melanocortin agonist treatment on food intake in rhesus macaques. These are exploratory studies to optimize dose given s.c. Phase 2 will determine if chronic eripheral melanocortin agonist treatment can reduce body weight and adiposity in diet-induced obese (DIO) monkeys. This study will also determine if changes in body weight are do to chronic changes in caloric intake and/or increased energy expenditure. Finally, these studies will determine if this chronic melanocortin treatment improves glucose homeostasis and cardiovascular function. These are extensive studies that will generate critical insight into the potential of melanocortin agonist as a therapy for human obesity and diabetes.